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1.
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2.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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3.
  • Kehoe, Laura, et al. (författare)
  • Make EU trade with Brazil sustainable
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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4.
  • Hatti, Neelambar, et al. (författare)
  • Economists and Poverty : Introduction
  • 2005
  • Ingår i: Economists and Poverty : From Adam Smith to Amartya Sen - From Adam Smith to Amartya Sen. - 8179360164 ; , s. 1-18
  • Bokkapitel (refereegranskat)
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5.
  • Holmes, Michael V., et al. (författare)
  • Secretory Phospholipase A(2)-IIA and Cardiovascular Disease
  • 2013
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:21, s. 1966-1976
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
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6.
  • Alamidi, Daniel, et al. (författare)
  • T1 Relaxation Time in Lungs of Asymptomatic Smokers.
  • 2016
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Interest in using T1 as a potential MRI biomarker of chronic obstructive pulmonary disease (COPD) has recently increased. Since tobacco smoking is the major risk factor for development of COPD, the aim for this study was to examine whether tobacco smoking, pack-years (PY), influenced T1 of the lung parenchyma in asymptomatic current smokers.
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7.
  • Alamidi, Daniel, et al. (författare)
  • Variable Flip Angle 3D Ultrashort Echo Time (UTE) T-1 Mapping of Mouse Lung: A Repeatability Assessment
  • 2018
  • Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 48:3, s. 846-852
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lung T-1 is a potential translational biomarker of lung disease. The precision and repeatability of variable flip angle (VFA) T-1 mapping using modern 3D ultrashort echo time (UTE) imaging of the whole lung needs to be established before it can be used to assess response to disease and therapy. Purpose: To evaluate the feasibility of regional lung T-1 quantification with VFA 3D-UTE and to investigate long-and short-term T-1 repeatability in the lungs of naive mice. Field strength/Sequence: 3D free-breathing radial UTE (8 mu s) at 4.7T. Assessment: VFA 3D-UTE T-1 calculations were validated against T-1 values measured with inversion recovery (IR) in phantoms. Lung T-1 and proton density (S-0) measurements of whole lung and muscle were repeated five times over 1 month in free-breathing naive mice. Two consecutive T-1 measurements were performed during one of the imaging sessions. Statistical Tests: Agreement in T-1 between VFA 3D-UTE and IR in phantoms was assessed using Bland-Altman and Pearson's correlation analysis. The T-1 repeatability in mice was evaluated using coefficient of variation (CV), repeated-measures analysis of variance (ANOVA), and paired t-test. Results: Good T-1 agreement between the VFA 3D-UTE and IR methods was found in phantoms. T-1 in lung and muscle showed a 5% and 3% CV (1255 +/- 63 msec and 1432 +/- 42 msec, respectively, mean +/- SD) with no changes in T-1 or S-0 over a month. Consecutive measurements resulted in an increase of 2% in both lung T-1 and S-0. Data Conclusion: VFA 3D-UTE shows promise as a reliable T-1 mapping method that enables full lung coverage, high signal-to-noise ratio (similar to 25), and spatial resolution (300 mu m) in freely breathing animals. The precision of the VFA 3D-UTE method will enable better design and powering of studies.
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8.
  • Arai, Sally, et al. (författare)
  • Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation : a report from the Center for International Blood and Marrow Transplant Research.
  • 2015
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 21:2, s. 266-74
  • Tidskriftsartikel (refereegranskat)abstract
    • Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P < .0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research.
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9.
  • Arlien-Soborg, Mai C., et al. (författare)
  • Acromegaly management in the Nordic countries: A Delphi consensus survey
  • 2024
  • Ingår i: Clinical Endocrinology. - : WILEY. - 0300-0664 .- 1365-2265.
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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10.
  • Arlien-Soborg, Mai C., et al. (författare)
  • Acromegaly management in the Nordic countries: A Delphi consensus survey
  • 2024
  • Ingår i: CLINICAL ENDOCRINOLOGY. - : WILEY. - 0300-0664 .- 1365-2265.
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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11.
  • Azevedo, Flavio, et al. (författare)
  • Social and moral psychology of COVID-19 across 69 countries
  • 2023
  • Ingår i: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
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12.
  • Bärring, Maja, 1988, et al. (författare)
  • A VSM Approach to Support Data Collection for a Simulation Model
  • 2017
  • Ingår i: Proceedings - Winter Simulation Conference. - 0891-7736. ; , s. 3928-3939
  • Konferensbidrag (refereegranskat)abstract
    • Simulation is a powerful tool to analyze and help in the decision making process of a production system. It is capable of delivering a dynamic analysis, both of the existing system and the future planned system. One major challenge with simulation projects however, is the time required at the initial stage when collecting data. For this study, Value Stream Mapping (VSM) has been selected as a complementary method for the data collection. VSM has been widely spread in industry, and it is a suitable method for identifying value streams and visualizing flows. In this study, the applicability of VSM for data collection is examined for a production system with complex and non-linear flows. The results of this study confirms that VSM can support in the data collection phase, but entails the support from subject matters.
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13.
  • Grut, Viktor, et al. (författare)
  • Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis : a presymptomatic case-control study
  • 2021
  • Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 28:9, s. 3072-3079
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Epstein-Barr virus (EBV) and Human herpesvirus 6A (HHV-6A) are associated with increased risk of multiple sclerosis (MS). Conversely, infection with Cytomegalovirus (CMV) has been suggested to reduce the risk of MS but supporting data from presymptomatic studies are lacking. Here, we sought to increase the understanding of CMV in MS aetiology.METHODS: We performed a nested case-control study with presymptomatically collected blood samples identified through cross-linkage of MS registries and Swedish biobanks. Serological antibody response against CMV, EBV and HHV-6A was determined using a bead-based multiplex assay. Odds ratio (OR) with 95 % confidence intervals (CI) for CMV seropositivity as risk factor for MS was calculated by conditional logistic regression and adjusted for EBV and HHV-6A seropositivity. Potential interactions on the additive scale were analysed by calculating attributable proportion due to interaction (AP).RESULTS: Serum samples from 670 pairs of matched cases and controls were included. CMV seropositivity was associated with a reduced risk for MS (OR = 0.70, 95% CI 0.56-0.88, p = 0.003). Statistical interactions on the additive scale were observed between seronegativity for CMV and seropositivity against HHV-6A (AP 0.34, 95% CI 0.06-0.61) and EBV antigen EBNA-1 (amino acid 385-420) at age 20-39 years (AP 0.37, 95% CI 0.09-0.65).CONCLUSIONS: CMV seropositivity is associated with a decreased risk for MS. The protective role for CMV infection in MS aetiology is further supported by the interactions between CMV seronegativity and EBV and HHV-6A seropositivity.
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14.
  • Lesén, Eva, et al. (författare)
  • Comorbidities, treatment patterns and cost-of-illness of acromegaly in Sweden: a register-linkage population-based study.
  • 2017
  • Ingår i: European journal of endocrinology. - 1479-683X. ; 176:2, s. 203-212
  • Tidskriftsartikel (refereegranskat)abstract
    • Acromegaly is a complex endocrine disease with multiple comorbidities. Treatment to obtain biochemical remission includes surgery, medical therapy and radiation. We aimed to describe comorbidities, treatment patterns and cost-of-illness in patients with acromegaly in Sweden.A nationwide population-based study.Patients with acromegaly were identified and followed in national registers in Sweden. Longitudinal treatment patterns were assessed in patients diagnosed between July 2005 and December 2013. The cost-of-illness during 2013 was estimated from a societal perspective among patients diagnosed between 1987 and 2013.Among 358 patients with acromegaly (48% men, mean age at diagnosis 50.0 (s.d. 15.3) years) at least one comorbidity was reported in 81% (n=290). The most common comorbidities were hypertension (40%, n=142), neoplasms outside the pituitary (30%, n=109), hypopituitarism (22%, n=80) and diabetes mellitus (17%, n=61). Acromegaly treatment was initiated on average 3.7 (s.d. 6.9) months after diagnosis. Among the 301 treated patients, the most common first-line treatments were surgery (60%, n=180), somatostatin analogues (21%, n=64) and dopamine agonists (14%, n=41). After primary surgery, 24% (n=44) received somatostatin analogues. The annual per-patient cost was €12000; this was €8700 and €16000 if diagnosed before or after July 2005, respectively. The cost-of-illness for acromegaly and its comorbidities was 77% from direct costs and 23% from production loss.The prevalence of comorbidity is high in patients with acromegaly. The most common first-line treatment in acromegalic patients was surgery followed by somatostatin analogues. The annual per-patient cost of acromegaly and its comorbidities was €12000.
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15.
  • Liljander, Anne, et al. (författare)
  • Influences of intermittent preventive treatment and persistent multiclonal Plasmodium falciparum infections on clinical malaria risk
  • 2010
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:10
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Intermittent preventive treatment (IPT) of malaria involves administration of curative doses of antimalarials at specified time points to vulnerable populations in endemic areas, regardless whether a subject is known to be infected. The effect of this new intervention on the development and maintenance of protective immunity needs further understanding. We have investigated how seasonal IPT affects the genetic diversity of Plasmodium falciparum infections and the risk of subsequent clinical malaria.MATERIAL AND METHODS: The study included 2227 Ghanaian children (3-59 months) who were given sulphadoxine-pyrimethamine (SP) bimonthly, artesunate plus amodiaquine (AS+AQ) monthly or bimonthly, or placebo monthly for six months spanning the malaria transmission season. Blood samples collected at three post-interventional surveys were analysed by genotyping of the polymorphic merozoite surface protein 2 gene. Malaria morbidity and anaemia was monitored during 12 months follow-up.RESULTS: Monthly IPT with AS+AQ resulted in a marked reduction in number of concurrent clones and only children parasite negative just after the intervention period developed clinical malaria during follow-up. In the placebo group, children without parasites as well as those infected with ≥2 clones had a reduced risk of subsequent malaria. The bimonthly SP or AS+AQ groups had similar number of clones as placebo after intervention; however, diversity and parasite negativity did not predict the risk of malaria. An interaction effect showed that multiclonal infections were only associated with protection in children without intermittent treatment.CONCLUSION: Molecular typing revealed effects of the intervention not detected by ordinary microscopy. Effective seasonal IPT temporarily reduced the prevalence and genetic diversity of P. falciparum infections. The reduced risk of malaria in children with multiclonal infections only seen in untreated children suggests that persistence of antigenically diverse P. falciparum infections is important for the maintenance of protective malaria immunity in high transmission settings.
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16.
  • Lu, Yingchang, et al. (författare)
  • A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk.
  • 2018
  • Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:18, s. 5419-5430
  • Tidskriftsartikel (refereegranskat)abstract
    • .AbstractLarge-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.
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17.
  • Machiela, Mitchell J., et al. (författare)
  • Characterization of Large Structural Genetic Mosaicism in Human Autosomes
  • 2015
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
  • Tidskriftsartikel (refereegranskat)abstract
    • Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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18.
  • Mehta, Rohtesh S., et al. (författare)
  • Composite GRFS and CRFS Outcomes After Adult Alternative Donor HCT
  • 2020
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 38:18, s. 2062-2076
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]-bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor.METHODS We report composite end points of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) and chronic GVHD (cGVHD)-free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant.RESULTS In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group.CONCLUSION Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.
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19.
  • Mehta, Rohtesh S., et al. (författare)
  • GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia
  • 2019
  • Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 3:9, s. 1441-1449
  • Tidskriftsartikel (refereegranskat)abstract
    • We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P < .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P < .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors.
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20.
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21.
  • Nikiforow, Sarah, et al. (författare)
  • Upper gastrointestinal acute graft-versus-host disease adds minimal prognostic value in isolation or with other graft-versus-host disease symptoms as currently diagnosed and treated.
  • 2018
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 103:10, s. 1708-1719
  • Tidskriftsartikel (refereegranskat)abstract
    • Upper gastrointestinal acute graft-versus-host disease is reported in approximately 30% of hematopoietic stem cell transplant recipients developing acute graft-versus-host disease. Currently classified as Grade II in consensus criteria, upper gastrointestinal acute graft-versus-host disease is often treated with systemic immunosuppression. We reviewed the Center for International Blood and Marrow Transplant Research database to assess the prognostic implications of upper gastrointestinal acute graft-versus-host disease in isolation or with other acute graft-versus-host disease manifestations. 8567 adult recipients of myeloablative allogeneic hematopoietic stem cell transplant receiving T-cell replete grafts for acute leukemia, chronic myeloid leukemia or myelodysplastic syndrome between 2000 and 2012 were analyzed. 51% of transplants were from unrelated donors. Reported upper gastrointestinal acute graft-versus-host disease incidence was 12.1%; 2.7% of recipients had isolated upper gastrointestinal acute graft-versus-host disease, of whom 95% received systemic steroids. Patients with isolated upper gastrointestinal involvement had similar survival, disease-free survival, transplant-related mortality, and relapse as patients with Grades 0, I, or II acute graft-versus-host disease. Unrelated donor recipients with isolated upper gastrointestinal acute graft-versus-host disease had less subsequent chronic graft-versus-host disease than those with Grades I or II disease (P=0.016 and P=0.0004, respectively). Upper gastrointestinal involvement added no significant prognostic information when present in addition to other manifestations of Grades I or II acute graft-versus-host disease. If upper gastrointestinal symptoms were reclassified as Grade 0 or I, 425 of 2083 patients (20.4%) with Grade II disease would be downgraded, potentially impacting the interpretation of clinical trial outcomes. Defining upper gastrointestinal acute graft-versus-host disease as a Grade II entity, as it is currently diagnosed and treated, is not strongly supported by this analysis. The general approach to diagnosis, treatment and grading of upper gastrointestinal symptoms and their impact on subsequent acute graft-versus-host disease therapy warrants reevaluation.
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22.
  • Oddsson, Asmundur, et al. (författare)
  • Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
  • 2023
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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23.
  • Papakokkinou, Eleni, et al. (författare)
  • Excess Morbidity Persists in Patients With Cushing’s Disease During Long-term Remission : A Swedish Nationwide Study
  • 2020
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - Washington : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:8, s. 2616-2624
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Whether multisystem morbidity in Cushing's disease (CD) remains elevated during long-term remission is still undetermined.Objective: To investigate comorbidities in patients with CD.Design, setting, and patients: A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status.Main outcomes: Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission.Results: We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission.Conclusion: Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
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24.
  • Ragnarsson, Oskar, 1971, et al. (författare)
  • Overall and Disease-Specific Mortality in Patients With Cushing Disease: A Swedish Nationwide Study
  • 2019
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 104:6, s. 2375-2384
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable. Objective: To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD. Design, Patients, and Methods: A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality. Results: Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome. Conclusion: Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.
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25.
  • Ragnarsson, Oskar, 1971, et al. (författare)
  • The incidence of Cushing’s disease : a nationwide Swedish study
  • 2019
  • Ingår i: Pituitary. - : Springer. - 1386-341X .- 1573-7403. ; 22:2, s. 179-186
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies on the incidence of Cushing’s disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden.Methods: Patients registered with a diagnostic code for Cushing’s syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data.Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4–1.8) cases per million. 1987–1995, 1996–2004, and 2005–2013, the mean annual incidence was 1.5 (1.1–1.8), 1.4 (1.0–1.7) and 2.0 (1.7–2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05).Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987–2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.
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26.
  • Shu, Xiang, et al. (författare)
  • Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
  • 2019
  • Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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27.
  • Spikol, Daniel (creator_code:cre_t, creator_code:res_t)
  • Forskarnas galleri #5 : People have the power: IOTAP on exhibit
  • 2018
  • Konstnärligt arbeteabstract
    • Överallt samlar sensorer data som analyseras för att räkna ut hur man sparar energi, hur mycket insulin som ska injiceras, var den närmaste hyrbilen finns, hur många människor som fortfarande är kvar inne i en brinnande byggnad... Denna snabba spridning av teknik kallas för Sakernas Internet, eller IoT. Människor har makten, eller har vi verkligen det? Hur mycket värderar vi vår integritet? Vilka internetanslutna gadgets hjälper oss att leva ett hälsosamt och hållbart liv - och vilka prylar kommer bara att öka vår stressnivå? När blir användningen missbruk? Utställningen undersöker hur IoT påverkar människor, samhälle och industri. Forskningsprojekt i utställningen: Emergent Configuration for IoT Systems (ECOS+), Smart energy management and security (SEMS), Fair Data, Walk the ward, Dynamic Intelligent Sensor-Intensive Systems (DISS), PELARS-projektet och Busrunner presenteras i "IOTAP-labbet"
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28.
  • Söderholm, Martin, et al. (författare)
  • Genome-wide association meta-analysis of functional outcome after ischemic stroke
  • 2019
  • Ingår i: Neurology. - 1526-632X. ; 92:12, s. 1271-1283
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To discover common genetic variants associated with poststroke outcomes using a genome-wide association (GWA) study. METHODS: The study comprised 6,165 patients with ischemic stroke from 12 studies in Europe, the United States, and Australia included in the GISCOME (Genetics of Ischaemic Stroke Functional Outcome) network. The primary outcome was modified Rankin Scale score after 60 to 190 days, evaluated as 2 dichotomous variables (0-2 vs 3-6 and 0-1 vs 2-6) and subsequently as an ordinal variable. GWA analyses were performed in each study independently and results were meta-analyzed. Analyses were adjusted for age, sex, stroke severity (baseline NIH Stroke Scale score), and ancestry. The significance level was p < 5 × 10-8. RESULTS: We identified one genetic variant associated with functional outcome with genome-wide significance (modified Rankin Scale scores 0-2 vs 3-6, p = 5.3 × 10-9). This intronic variant (rs1842681) in the LOC105372028 gene is a previously reported trans-expression quantitative trait locus for PPP1R21, which encodes a regulatory subunit of protein phosphatase 1. This ubiquitous phosphatase is implicated in brain functions such as brain plasticity. Several variants detected in this study demonstrated suggestive association with outcome (p < 10-5), some of which are within or near genes with experimental evidence of influence on ischemic stroke volume and/or brain recovery (e.g., NTN4, TEK, and PTCH1). CONCLUSIONS: In this large GWA study on functional outcome after ischemic stroke, we report one significant variant and several variants with suggestive association to outcome 3 months after stroke onset with plausible mechanistic links to poststroke recovery. Future replication studies and exploration of potential functional mechanisms for identified genetic variants are warranted.
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29.
  • Van Bavel, Jay J., et al. (författare)
  • National identity predicts public health support during a global pandemic
  • 2022
  • Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic. Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.
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30.
  • Vouzouneraki, Konstantina, et al. (författare)
  • Carpal tunnel syndrome in acromegaly: a nationwide study.
  • 2021
  • Ingår i: European journal of endocrinology. - : Bioscientifica. - 1479-683X .- 0804-4643. ; 184:2, s. 209-216
  • Tidskriftsartikel (refereegranskat)abstract
    • Carpal tunnel syndrome (CTS) is common in patients with acromegaly, with a reported prevalence of 19-64%. We studied CTS in a large national cohort of patients with acromegaly and the temporal relationship between the two diagnoses.Retrospective, nationwide, cohort study including patients diagnosed with acromegaly in Sweden, 2005-2017, identified in the Swedish Healthcare Registries.CTS (diagnosis and surgery in specialised healthcare) was analysed from 8.5 years before the diagnosis of acromegaly until death or end of the study. Standardised incidence ratios (SIRs) with 95% confidence intervals were calculated for CTS with the Swedish population as reference.The analysis included 556 patients with acromegaly (50% women) diagnosed at mean (SD) age 50.1 (15.0) years. During the study period, 48 patients were diagnosed with CTS and 41 patients underwent at least one CTS surgery. Among the latter group, 35 (85%) were operated for CTS before the acromegaly diagnosis; mean interval (range) 2.2 (0.3-8.5) years and the SIR for having CTS surgery before the diagnosis of acromegaly was 6.6 (4.8-8.9). Women with acromegaly had a higher risk for CTS than men (hazard ratio 2.5, 95% CI 1.3-4.7).Patients with acromegaly had a 6-fold higher incidence for CTS surgery before the diagnosis of acromegaly compared with the general population. The majority of patients with both diagnoses were diagnosed with CTS prior to acromegaly. Increased awareness of signs of acromegaly in patients with CTS might help to shorten the diagnostic delay in acromegaly, especially in women.
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31.
  • Vågberg, Daniel, 1983-, et al. (författare)
  • Finite-Size Scaling at the Jamming Transition : Corrections to Scaling and the Correlation-Length Critical Exponent
  • 2011
  • Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics. - : American Physical Society. - 1539-3755 .- 1550-2376. ; 83:3, s. 030303-
  • Tidskriftsartikel (refereegranskat)abstract
    • We carry out a finite-size scaling analysis of the jamming transition in frictionless bidisperse soft core disks in two dimensions. We consider two different jamming protocols: (i) quench from random initial positions and (ii) quasistatic shearing. By considering the fraction of jammed states as a function of packing fraction for systems with different numbers of particles, we determine the spatial correlation length critical exponent ν≈1 and show that corrections to scaling are crucial for analyzing the data. We show that earlier numerical results yielding ν<1 are due to the improper neglect of these corrections.
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32.
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33.
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34.
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35.
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36.
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37.
  • Agardh, Daniel, et al. (författare)
  • HLA-DQB1*0201/0302 is associated with severe retinopathy in patients with IDDM
  • 1996
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 39:11, s. 1313-1317
  • Tidskriftsartikel (refereegranskat)abstract
    • Some insulin-dependent diabetic (IDDM) patients develop severe forms of retinopathy. Putative risk factors such as hypertension, poor metabolic control, nephropathy and growth hormone levels do not fully explain the progress of retinopathy in these patients. It has been discussed whether there is a genetic marker, since some diabetic patients without any known predisposing risk factors develop severe retinopathy and others do not. In the present study, HLA-DR and DQ were compared in two patient groups with IDDM. One group consisted of patients with early-onset diabetes, with severe non-proliferative or proliferative retinopathy; the other group had no or only mild signs of retinopathy. High resolution HLA typing was carried out by polymerase chain reaction (PCR) and hybridization with allele specific probes. Alleles on the DR3-DQ2 haplotype, DRB1*0301, DQA1*0501 and DQB1*0201, were more frequent in patients with severe retinopathy. A difference was seen when combining certain alleles in the genotypes of DQA1*03/0501 (p > 0.05) and DQB1*0201/0302 (p < 0.01). The findings of the present study suggest that DQB1*0201/0302 is the strongest genetic marker for severe retinopathy and DRB1*0301/0401 only has a secondary influence when combined with this genotype. It seems as if IDDM patients who are positive for the genotype DR3-DQ2/DR4-DQ8 (DRB1*0301-DQA1*0501-DQB1*0201/DRB1*0401 -DQA1*03-DQB1*0302) are at greater risk of developing severe retinopathy.
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38.
  • Agardh, Daniel, et al. (författare)
  • Inverse relationship between GAD65 antibody levels and severe retinopathy in younger type 1 diabetic patients
  • 1998
  • Ingår i: Diabetes Research and Clinical Practice. - 1872-8227. ; 40:1, s. 9-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Several risk factors for severe non-proliferative and proliferative retinopathy in type 1 diabetes mellitus have been proposed without explaining the rapid progression of retinopathy in some patients. Since GAD65 autoantibodies (GAD65Abs) are detected against glutamic acid decarboxylase (GAD), which is mainly expressed in islets and nervous tissue in type 1 diabetic patients, the aim of the present investigation was to test the hypothesis whether GAD65Abs are associated with rapidly progressing severe retinopathy. Patients with severe non-proliferative or proliferative retinopathy (n = 27) were compared with another group, which in spite of long diabetes duration had no or only mild signs of retinopathy (n = 28). GAD65Abs were analysed in a radioimmunoassay using in vitro translated human GAD65, and the levels were expressed as an index in relation to positive and negative reference samples. Using a cut-off level representing the 99th percentile of normals, 6/27 (22%) with and 9/28 (32%) without severe retinopathy were considered GAD65Ab positive. Although there was no difference in the number of GAD65Ab positive patients, the GAD65Ab levels were lower in patients with (0.30; 0.11-0.64) than without (0.68; 0.34-1.12) severe retinopathy (P = 0.03). The patients were also subjected to HLA-DR and DQ typing by PCR and hybridization with oligospecific probes. DQ2/8 was more common in patients with (56%) than without (29%) severe retinopathy (P = 0.05), but DQ2/8 could not account for the lower GAD65Ab levels in patients with severe retinopathy. It is concluded that GAD65Ab levels are inversely correlated with severe retinopathy in young type 1 diabetic patients.
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39.
  • Ahlberg, Erik, et al. (författare)
  • "Vi klimatforskare stödjer Greta och skolungdomarna"
  • 2019
  • Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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40.
  • Ahlström, Christoffer, et al. (författare)
  • Optimus Pråm - Semi-submersible wind farm installation vessel for Blekinge Offshore
  • 2014
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • In Sweden the government is investing lots of resources in order to meet the energy need with clean and renewable alternatives. Since wind is an unlimited source of energy the exploitations of wind farms is of great interest. This report describes a conceptual design of an innovative offshore wind turbine installation vessel for inland sea conditions, with highest possible energy efficiency and environmental friendly performance in every detail. The customer, Blekinge Offshore, main requirement is to receive a concept with an as low installation cost as possible.The final concept Optimus Pråm includes one installation vessel, which is a semi-submersible barge, and one support vessel that supply the installation vessel with power and propulsion. The power is distributed from the support vessel to the installation vessel through a power cable. The installation vessel will be self-propelled during the installation phase using electrical motors and thrusters.The installation vessel shall be able to handle gravity foundations and fully assembled wind turbines, transported vertically to the installation site. Foundations and windmills will be fully assembled in Karlshamn port before transit to site. During transit the installation and support vessel are connected to each other in all motions except pitch. This almost total fixed connection makes the two vessels acts like one, which gives the joint vessel excellent manoeuvrability. When installing foundations, the installation vessel and the support vessel disconnect. The installation vessel places the foundation at the planned location by ballasting until the foundation has reached the seabed. After de-ballasting the installation vessel and support vessel connects again and transit back to the harbour. When installing wind turbines the two vessels are kept connected and makes highly accurate positioning for the installation possible
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41.
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42.
  • Ahmadpanah, Seyed Mohammad Mehdi, 1996, et al. (författare)
  • SandTrap : Securing javascript-driven trigger-action platforms
  • 2021
  • Ingår i: Proceedings of the 30th USENIX Security Symposium. - : USENIX Association. - 9781939133243 ; , s. 2899-2916
  • Konferensbidrag (refereegranskat)abstract
    • Trigger-Action Platforms (TAPs) seamlessly connect a wide variety of otherwise unconnected devices and services, ranging from IoT devices to cloud services and social networks. TAPs raise critical security and privacy concerns because a TAP is effectively a “person-in-the-middle” between trigger and action services. Third-party code, routinely deployed as “apps” on TAPs, further exacerbates these concerns. This paper focuses on JavaScript-driven TAPs. We show that the popular IFTTT and Zapier platforms and an open-source alternative Node-RED are susceptible to attacks ranging from exfiltrating data from unsuspecting users to taking over the entire platform. We report on the changes by the platforms in response to our findings and present an empirical study to assess the implications for Node-RED. Motivated by the need for a secure yet flexible way to integrate third-party JavaScript apps, we propose SandTrap, a novel JavaScript monitor that securely combines the Node.js vm module with fully structural proxy-based two-sided membranes to enforce fine-grained access control policies. To aid developers, SandTrap includes a policy generation mechanism. We instantiate SandTrap to IFTTT, Zapier, and Node-RED and illustrate on a set of benchmarks how SandTrap enforces a variety of policies while incurring a tolerable runtime overhead. 
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43.
  • Ahmadpanah, Seyed Mohammad Mehdi, 1996, et al. (författare)
  • Securing Node-RED Applications
  • 2021
  • Ingår i: Protocols, Strands, and LogicEssays Dedicated to Joshua Guttman on the Occasion of his 66.66th Birthday. - Cham : Springer Science and Business Media Deutschland GmbH. ; , s. 1-21, s. 1-21, s. 1-21
  • Konferensbidrag (refereegranskat)abstract
    • Trigger-Action Platforms (TAPs) play a vital role in fulfilling the promise of the Internet of Things (IoT) by seamlessly connecting otherwise unconnected devices and services. While enabling novel and exciting applications across a variety of services, security and privacy issues must be taken into consideration because TAPs essentially act as persons-in-the-middle between trigger and action services. The issue is further aggravated since the triggers and actions on TAPs are mostly provided by third parties extending the trust beyond the platform providers. Node-RED, an open-source JavaScript-driven TAP, provides the opportunity for users to effortlessly employ and link nodes via a graphical user interface. Being built upon Node.js, third-party developers can extend the platform’s functionality through publishing nodes and their wirings, known as flows. This paper proposes an essential model for Node-RED, suitable to reason about nodes and flows, be they benign, vulnerable, or malicious. We expand on attacks discovered in recent work, ranging from exfiltrating data from unsuspecting users to taking over the entire platform by misusing sensitive APIs within nodes. We present a formalization of a runtime monitoring framework for a core language that soundly and transparently enforces fine-grained allowlist policies at module-, API-, value-, and context-level. We introduce the monitoring framework for Node-RED that isolates nodes while permitting them to communicate via well-defined API calls complying with the policy specified for each node.
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44.
  • Al-Shamkhi, Nasrin, 1985-, et al. (författare)
  • Pituitary function before and after surgery for nonfunctioning pituitary adenomas-data from the Swedish Pituitary Register.
  • 2023
  • Ingår i: European journal of endocrinology. - : Bioscientifica. - 1479-683X .- 0804-4643. ; 189:2, s. 217-224
  • Tidskriftsartikel (refereegranskat)abstract
    • Data on pre- and postoperative pituitary function in nonfunctioning pituitary adenomas (NFPA) are not consistent. We aimed to investigate pituitary function before and up to 5 years after transsphenoidal surgery with emphasis on the hypothalamic-pituitary-adrenal axis (HPA).Data from the Swedish Pituitary Register was used to analyze anterior pituitary function in 838 patients with NFPA diagnosed between 1991 and 2014. Patients who were reoperated or had received radiotherapy were excluded.Preoperative ACTH, TSH, LH/FSH, and GH deficiencies were reported in 31% (236/755), 39% (300/769), 51% (378/742), and 28% (170/604) of the patients, respectively. Preoperative median tumor volume was 5.0 (2.4-9.0) cm3. Among patients with preoperative, 1 year and 5 years postoperative data on the HPA axis (n = 428), 125 (29%) were ACTH-deficient preoperatively. One year postoperatively, 26% (32/125) of them had recovered ACTH function while 23% (70/303) patients had developed new ACTH deficiency. Thus, 1 year postoperatively, 163 (38%) patients were ACTH-deficient (P < .001 vs. preoperatively). No further increase was seen 5 years postoperatively (36%, P = .096). At 1 year postoperatively, recoveries in the TSH and LH/FSH axes were reported in 14% (33/241) and 15% (46/310), respectively, and new deficiencies in 22% (88/403) and 29% (83/288), respectively.Adrenocorticotrophic hormone deficiency increased significantly at 1 year postoperatively. Even though not significant, some patients recovered from or developed new deficiency between 1 and 5 years postoperatively. This pattern was seen in all axes. Our study emphasizes that continuous individual evaluations are needed during longer follow-up of patients operated for NFPA.
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45.
  • Alamidi, Daniel, et al. (författare)
  • COPD Patients Have Short Lung Magnetic Resonance T1 Relaxation Time.
  • 2016
  • Ingår i: COPD. - : Informa UK Limited. - 1541-2563 .- 1541-2555. ; 13:2, s. 153-159
  • Tidskriftsartikel (refereegranskat)abstract
    • Magnetic resonance imaging (MRI) may provide attractive biomarkers for assessment of pulmonary disease in clinical trials as it is free from ionizing radiation, minimally invasive and allows regional information. The aim of this study was to characterize lung MRI T1 relaxation time as a biomarker of chronic obstructive pulmonary disease (COPD); and specifically its relationship to smoking history, computed tomography (CT), and pulmonary function test (PFT) measurements in comparison to healthy age-matched controls. Lung T1 and inter-quartile range (IQR) of T1 maps from 24 COPD subjects and 12 healthy age-matched non-smokers were retrospectively analyzed from an institutional review board approved study. The subjects underwent PFTs and two separate MR imaging sessions at 1.5 tesla to test T1 repeatability. CT scans were performed on the COPD subjects. T1 repeatability (intraclass correlation coefficient) was 0.72 for repeated scans acquired on two visits. The lung T1 was significantly shorter (p < 0.0001) and T1 IQR was significantly larger (p = 0.0002) for the COPD subjects compared to healthy controls. Lung T1 significantly (p = 0.001) correlated with lung density assessed with CT. Strong significant correlations (p < 0.0001) between lung T1 and all PFT measurements were observed. Cigarette exposure did not correlate with lung T1 in COPD subjects. In conclusion, lung MRI T1 mapping shows potential as a repeatable, radiation free, non-invasive imaging technique in the evaluation of COPD.
  •  
46.
  • Alström, Per, et al. (författare)
  • Discovery of a relict lineage and monotypic family of passerine birds.
  • 2014
  • Ingår i: Biology Letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 10:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Analysis of one of the most comprehensive datasets to date of the largest passerine bird clade, Passerida, identified 10 primary well-supported lineages corresponding to Sylvioidea, Muscicapoidea, Certhioidea, Passeroidea, the ‘bombycillids’ (here proposed to be recognized as Bombycilloidea), Paridae/Remizidae (proposed to be recognized as Paroidea), Stenostiridae, Hyliotidae, Regulidae (proposed to be recognized as Reguloidea) and spotted wren-babbler Spelaeornis formosus. The latter was found on a single branch in a strongly supported clade with Muscicapoidea, Certhioidea and Bombycilloidea, although the relationships among these were unresolved. We conclude that the spotted wren-babbler represents a relict basal lineage within Passerida with no close extant relatives, and we support the already used name Elachura formosa and propose the new family name Elachuridae for this single species.
  •  
47.
  • Altman, Daniel, et al. (författare)
  • Anal sphincter lacerations and upright delivery postures - a risk analysis from a randomized controlled trial
  • 2007
  • Ingår i: International Urogynecology Journal. - : Springer Science and Business Media LLC. - 0937-3462 .- 1433-3023. ; 18:2, s. 141-146
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To evaluate obstetric sphincter lacerations after a kneeling or sitting position at second stage of labor in a multivariate risk analysis model. MATERIALS AND METHODS: Two hundred and seventy-one primiparous women with normal pregnancies and spontaneous labor were randomized, 138 to a kneeling position and 133 to a sitting position. Medical data were retrieved from delivery charts and partograms. Risk factors were tested in a multivariate logistic regression model in a stepwise manner. RESULTS: The trial was completed by 106 subjects in the kneeling group and 112 subjects in the sitting group. There were no significant differences with regard to duration of second stage of labor or pre-trial maternal characteristics between the two groups. Obstetrical sphincter tears did not differ significantly between the two groups but an intact perineum was more common in the kneeling group (p<0.03) and episiotomy (mediolateral) was more common in the sitting group (p<0.05). Three grade IV sphincter lacerations occurred in the sitting group compared to none in the kneeling group (NS). Multivariate risk analysis indicated that prolonged duration of second stage of labor and episiotomy were associated with an increased risk of third- or fourth-degree sphincter tears (p<0.01 and p<0.05, respectively). Delivery posture, maternal age, fetal weight, use of oxytocin, and use of epidural analgesia did not increase the risk of obstetrical anal sphincter lacerations in the two upright postures. CONCLUSION: Obstetrical anal sphincter lacerations did not differ significantly between a kneeling or sitting upright delivery posture. Episiotomy was more common after a sitting delivery posture, which may be associated with an increased risk of anal sphincter lacerations. Upright delivery postures may be encouraged in healthy women with normal, full-term pregnancy.
  •  
48.
  • Andersson, Agnes, et al. (författare)
  • Headache Before and After Endoscopic Transsphenoidal Pituitary Tumor Surgery: A Prospective Study
  • 2022
  • Ingår i: Journal of Neurological Surgery Part B-Skull Base. - : Georg Thieme Verlag KG. - 2193-6331 .- 2193-634X. ; 83:suppl. 2
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Headache is a common symptom among patients with pituitary tumors, as it is in the general population. The aim of the study was to investigate headache as a symptom in patients with pituitary tumors before and 6 months after endoscopic transsphenoidal surgery (TSS). Design This is a prospective observational cohort study. Setting This study was conducted at university tertiary referral hospital. Participants A total of 110 adult patients underwent endoscopic TSS for pituitary tumors. Main Outcome Measures The Migraine Disability Assessment (MIDAS) questionnaire was used before and 6 months after surgery for the assessment of headache. Clinical variables with potential influence on headache were analyzed. Results Sixty-eight (62%) patients experienced headaches at least once during the 3 months before surgery. Thirty (27%) patients reported disabling headache before surgery, with younger age being an independent associated factor ( p <0.001). In patients with disabling headache before surgery, the median (interquartile range) MIDAS score improved from 78 (27-168) to 16 (2-145; p =0.049), headache frequency decreased from 45 (20-81) to 14 (4-35) days ( p =0.009), and headache intensity decreased from 6 (5-8) to 5 (4-7) ( p =0.011) after surgery. In total, 16 of the 30 (53%) patients reported a clinically relevant improvement and five (17%) a clinically relevant worsening. Four (5%) patients developed new disabling headache. No predictor for postoperative improvement of headache was identified. Conclusion In this prospective study, the results show that disabling headache improves following endoscopic TSS in a subset of patients with pituitary tumors. However, no predictive factors for improvement could be identified.
  •  
49.
  • Andersson, Eva M., 1968, et al. (författare)
  • High exposure to perfluorinated compounds in drinking water and thyroid disease. A cohort study from Ronneby, Sweden
  • 2019
  • Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 176
  • Tidskriftsartikel (refereegranskat)abstract
    • Per- and polyfluoroalkyl substances (PFAS) are extremely persistent manmade substances. Apart from exposure through food and indoor air and dust, humans can be exposed through drinking water if the surface or groundwater is contaminated. In 2013 very high levels of PFOS and PFHxS were found in the drinking water from one of the two waterworks supplying the municipality of Ronneby, Sweden. A cohort was formed, including all individuals who had lived at least one year in Ronneby during the period 1980–2013 (ñ63,000). Each year, addresses that got their drinking water from the contaminated water works were identified. Through the Swedish personal identity number, each individual was linked to registers providing diagnoses and prescriptions for hyper- and hypothyroidism. In total, 16,150 individuals had ever been exposed. The hazard ratios did not indicate any excess risk of hyperthyroidism among those with contaminated water. For hypothyroidism, the risk of being prescribed medication was significantly increased among women with exposure during the mid part of the study period (but not men). However, the association with period of exposure was non-monotonic, so the significance is considered to be a chance finding. Our research was limited by the relatively simple exposure assessment.
  •  
50.
  • Andersson, Jonas, et al. (författare)
  • Left ventricular remodelling changes without concomitant loss of myocardial fat after long-term dietary intervention
  • 2016
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 216, s. 92-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Accumulation of myocardial triglycerides (MTG) is associated with impaired left ventricular (LV) remodelling and function in obese and diabetic subjects. The role of MTG accumulation in development of heart failure in this group of patients is unknown. Short-term studies suggest that diets that lead to weight loss could mobilize MTG, with a favourable effect on cardiac remodelling. In a 24-month, randomized, investigator-blinded study, we assessed the effect of two different diets and subsequent weight loss on cardiac function and MTG in postmenopausal women. Methods: Sixty-eight healthy postmenopausal women with body mass index [BMI] >= 27 kg/m(2) were randomized to an ad libitum Palaeolithic diet (PD) or a Nordic Nutrition Recommendation (NNR) diet for 24 months. Morphology, cardiac function, and MTG levels were measured using magnetic resonance (MR) scanning, including proton spectroscopy at baseline and 6 and 24 months. Results: Despite mean weight losses of 4.9 (1.0) kg (NNR) and 7.8 (1.1) kg (PD), the MTG content did not change over time (p = 0.98 in the NNR and p = 0.11 in the PD group at 24 months). Reduced left ventricular mass was observed in both diet groups over 24 months. Blood pressure was reduced at 6 months, but returned to baseline levels at 24 months. End diastolic volume, stroke volume, and cardiac output decreased over time. No differences between diet groups were observed. Conclusions: Diet intervention and moderate weight loss over 24 months improved LV remodelling but did not alter MTG levels in overweight/obese postmenopausal women. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  •  
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